A chronic anal fissure is a common perianal condition. This review aims to evaluate both existing and new therapies in the treatment of chronic fissures. Pharmacological therapies such as glyceryl trinitrate (GTN), Diltiazem ointment and Botulinum toxin provide a relatively non-invasive option, but with higher recurrence rates. Lateral sphincterotomy remains the gold standard for treatment. Anal dilatation has no role in treatment. New therapies include perineal support devices, Gonyautoxin injection, fissurectomy, fissurotomy, sphincterolysis, and flap procedures. Further research is required comparing these new therapies with existing established therapies. This paper recommends initial pharmacological therapy with GTN or Diltiazem ointment with Botulinum toxin as a possible second line pharmacological therapy. Perineal support may offer a new dimension in improving healing rates. Lateral sphincterotomy should be offered if pharmacological therapy fails. New therapies are not suitable as first line treatments, though they can be considered if conventional treatment fails.
Anal fissure; Innovative therapy; Glyceryl trinitrate; Lateral sphincterotomy; Diltiazem; Botulinum toxin; Perineal support device
New drugs and technologies for cancer treatment are being developed at a rate that has created a reimbursement crisis. This article discusses third-party concerns about this problem and describes generic criteria that have proven to be useful in assessing any new technology. It is equally important to discontinue funding of ineffective and obsolete therapies as it is to devise a strategy for identifying and encouraging the development of new therapy that will be both clinically useful and cost-effective. Examples are provided to show that these are not necessarily mutually exclusive goals. Off-label application of standard therapy as well as the funding of new cancer therapy are considered. High-dose chemotherapy with autologous stem-cell support for treatment of a variety of neoplasms has become a major reimbursement challenge. Other technologies such as autolymphocyte therapy and use of colony-stimulating factors are considered in detail. Finally, a process for deciding how to fund new cancer therapy is described.
The field of cellular therapy of cancer is moving quickly and the issues involved with its advancement are complex and wide ranging. The growing clinical applications and success of adoptive cellular therapy of cancer has been due to the rapid evolution of immunology, cancer biology, gene therapy and stem cell biology and the translation of advances in these fields from the research laboratory to the clinic. The continued development of this field is dependent on the exchange of ideas across these diverse disciplines, the testing of new ideas in the research laboratory and in animal models, the development of new cellular therapies and GMP methods to produce these therapies, and the testing of new adoptive cell therapies in clinical trials. The Summit on Cell Therapy for Cancer to held on November 1 and 2, 2011 at the National Institutes of Health (NIH) campus will include a mix of perspectives, concepts and ideas related to adoptive cellular therapy that are not normally presented together at any single meeting. This novel assembly will generate new ideas and new collaborations and possibly increase the rate of advancement of this field.
Data and ongoing research on new cytotoxic and targeted therapies for the treatment of patients with metastatic breast cancer are outlined, and new developments regarding approved but relatively new classes of cytotoxic and targeted agents and also new classes of targeted therapy that are undergoing clinical evaluation are highlighted.
Newer treatments have improved survival for patients with metastatic breast cancer over the last two decades, and a battery of new cytotoxic and targeted therapies is continuing to enhance this trend. This review outlines recent data and ongoing research in this area, by highlighting new developments (regarding approved but relatively new classes of cytotoxic and targeted agents) and also new classes of targeted therapy that are undergoing clinical evaluation. Mechanisms for synergy between agents are discussed where data are available, as is information on the rationale behind the development of agents that inhibit angiogenesis, DNA repair, histone deacetylases, heat shock proteins, or various signaling pathways in tumor proliferation. The abundance of clinical research surrounding anticancer agents, together with ongoing cancer biology research, is expected to further increase the available pool of therapeutic options for metastatic breast cancer. Concomitantly, in the absence of an effective targeted monotherapy, a better understanding of the interplay between biologic and cytotoxic anticancer agents will improve our ability to rationally design combination regimens with better efficacy and tolerability.
Metastatic breast cancer; Combination therapy; Targeted therapy; Monoclonal antibodies; Small-molecule inhibitors
This paper reviews the literature about first-line therapies for H. pylori infection in recent years. First-line therapies are facing a challenge because of increasing treatment failure due to elevated antibiotics resistance. Several new treatment strategies that recently emerged to overcome antibiotic resistance have been surveyed. Alternative first-line therapies include bismuth-containing quadruple therapy, sequential therapy, concomitant therapy, and hybrid therapy. Levofloxacin-based therapy shows impressive efficacy but might be employed as rescue treatment due to rapidly raising resistance. Rifabutin-based therapy is also regarded as a rescue therapy. Several factors including antibiotics resistance, patient compliance, and CYP 2C19 genotypes could influence the outcome. Clinicians should use antibiotics according to local reports. It is recommended that triple therapy should not be used in areas with high clarithromycin resistance or dual clarithromycin and metronidazole resistance.
Patellar tendinopathy is a chronic overuse injury of the patellar tendon that is especially prevalent in people who are involved in jumping activities. Extracorporeal Shockwave Therapy is a relatively new treatment modality for tendinopathies. It seems to be a safe and promising part of the rehabilitation program for patellar tendinopathy. Extracorporeal Shockwave Therapy originally used focused shockwaves. Several years ago a new kind of shockwave therapy was introduced: radial shockwave therapy. Studies that investigate the effectiveness of radial shockwave therapy as treatment for patellar tendinopathy are scarce. Therefore the aim of this study is to compare the effectiveness of focussed shockwave therapy and radial shockwave therapy as treatments for patellar tendinopathy.
The TOPSHOCK study (Tendinopathy Of Patella SHOCKwave) is a two-armed randomised controlled trial in which the effectiveness of focussed shockwave therapy and radial shockwave therapy are directly compared. Outcome assessors and patients are blinded as to which treatment is given. Patients undergo three sessions of either focused shockwave therapy or radial shockwave therapy at 1-week intervals, both in combination with eccentric decline squat training. Follow-up measurements are scheduled just before treatments 2 and 3, and 1, 4, 7 and 12 weeks after the final treatment. The main outcome measure is the Dutch VISA-P questionnaire, which asks for pain, function and sports participation in subjects with patellar tendinopathy. Secondary outcome measures are pain determined with a VAS during ADL, sports and decline squats, rating of subjective improvement and overall satisfaction with the treatment. Patients will also record their sports activities, pain during and after these activities, and concurrent medical treatment on a weekly basis in a web-based diary. Results will be analysed according to the intention-to-treat principle.
The TOPSHOCK study is the first randomised controlled trial that directly compares the effectiveness of focused shockwave therapy and radial shockwave therapy, both in combination with eccentric decline squat training, for treating patellar tendinopathy.
Trial registration number NTR2774.
Massage therapy has grown in popularity, yet little is known globally or in New Zealand about massage therapists and their practices.
Purpose and Setting:
The aims of this study were to describe the practice patterns of trained Massage New Zealand massage therapists in New Zealand private practice, with regard to therapist characteristics; practice modes and settings, and therapy characteristics; referral patterns; and massage therapy as an occupation.
Research Design and Participants:
A survey questionnaire was mailed to 66 trained massage therapist members of Massage New Zealand who were recruiting massage clients for a concurrent study of massage therapy culture.
Most massage therapists were women (83%), NZ European (76%), and holders of a massage diploma qualification (89%). Massage therapy was both a full- (58%) and part-time (42%) occupation, with the practice of massage therapy being the only source of employment for 70% of therapists. Nearly all therapists (94%) practiced massage for more than 40 weeks in the year, providing a median of 16 – 20 hours of direct client care per week. Most massage therapists worked in a “solo practice” (58%) and used a wide and active referral network. Almost all therapists treated musculoskeletal symptoms: the most common client issues or conditions treated were back pain/problem (99%), neck/shoulder pain/problem (99%), headache or migraine (99%), relaxation and stress reduction (96%), and regular recovery or maintenance massage (89%). The most frequent client fee per treatment was NZ$60 per hour in a clinic and NZ$1 per minute at a sports event or in the workplace. Therapeutic massage, relaxation massage, sports massage, and trigger-point therapy were the most common styles of massage therapy offered. Nearly all massage therapists (99%) undertook client assessment; 95% typically provided self-care recommendations; and 32% combined other complementary and alternative medicine therapies with their massage consultations.
This study provides new information about the practice of massage therapy by trained massage therapists. It will help to inform the massage industry and other health care providers, potential funders, and policymakers about the provision of massage therapy in the NZ health care system.
Complementary and alternative therapies; massage therapy; New Zealand; integrative care; practice patterns
Myocardial infarction (MI) is a lead cause of mortality in the Western world. Treatment of acute MI is focused on restoration of antegrade flow which inhibits further tissue loss, but does not restore function to damaged tissue. Chronic therapy for injured myocardial tissue involves medical therapy that attempts to minimize pathologic remodeling of the heart. End stage therapy for chronic heart failure (CHF) involves inotropic therapy to increase surviving cardiac myocyte function or mechanical augmentation of cardiac performance. Not until the point of heart transplantation, a limited resource at best, does therapy focus on the fundamental problem of needing to replace injured tissue with new contractile tissue. In this setting, the potential for stem cell therapy has garnered significant interest for its potential to regenerate or create new contractile cardiac tissue. While to date adult stem cell therapy in clinical trials has suggested potential benefit, there is waning belief that the approaches used to date lead to regeneration of cardiac tissue. As the literature has better defined the pathways involved in cardiac differentiation, preclinical studies have suggested that stem cell pretreatment to direct stem cell differentiation prior to stem cell transplantation may be a more efficacious strategy for inducing cardiac regeneration. Here we review the available literature on pre-transplantation conditioning of stem cells in an attempt to better understand stem cell behavior and their readiness in cell-based therapy for myocardial regeneration.
Stem cells; mesenchymal stem cells; in vitro lineage specification; myocardium infarct; cardiac differentiation; cardiac tissue recovery
Psychological outcome measures are evolving into measures that depict progress over time. Interval measurement during therapy has not previously been reported for a patient-generated measure in primary care. We aimed to determine the sensitivity to change throughout therapy, using ‘PSYCHLOPS’ (Psychological Outcome Profiles), and to determine if new problems appearing during therapy diminish overall improvement.
Responses to PSYCHLOPS, pre-, during- and post-therapy were compared. Setting: patients offered brief cognitive behaviour therapy in primary care in Poland.
238 patients completed the pre-therapy questionnaire, 194 (81.5%) the during-therapy questionnaire and 142 the post-therapy questionnaire (59.7%). For those completing all three questionnaires (n = 135), improvement in total scores produced an overall Effect Size of 3.1 (2.7 to 3.4). We estimated change using three methods for dealing with missing values. Single and multiple imputation did not significantly change the Effect Size; ‘Last Value Carried Forward’, the most conservative method, produced an overall Effect Size of 2.3 (1.9 to 2.6). New problems during therapy were reported by 81 patients (60.0%): new problem and original problem scores were of similar magnitude and change scores were not significantly different when compared to patients who did not report new problems.
A large proportion of outcome data is lost when outcome measures depend upon completed end of therapy questionnaires. The use of a during-therapy measure increases data capture. Missing data still produce difficulties in interpreting overall effect sizes for change. We found no evidence that new problems appearing during therapy hampered overall recovery.
Pegylated interferon and ribavirin combination therapy is accepted as the standard antiviral treatment for chronic hepatitis C regardless of HCV genotype. This combination therapy achieves higher response rates than previous therapy, but, nevertheless, a large proportion of patients suffer from treatment failure or adverse events. Recent clinical studies of viral kinetics during antiviral treatment have led to the introduction of response-guided therapy, the concept of 'customized therapy depending on viral response', which focuses on modulation of the treatment period depending on the viral response to create a sustained viral response without unnecessary medication and costs. New upcoming direct-acting antivirals (DAAs) maximize response rate, and triple therapy including DAAs along with pegylated interferon and ribavirin combination therapy could soon be the standard therapy. In this article, we reviewed the factors affecting treatment, response guided treatment, retreatment after failure of standard treatment, management of adverse events during treatment, and new treatment options.
Chronic hepatits C; Pegylated interferon; Ribavirin; Response-guided therapy
Gold nanotechnology driven recent approach opens up a new possibility for the destruction of cancer cells through photothermal therapy. Ultimately, photothermal therapy may enter into clinical therapy and as a result, there is an urgent need for techniques to monitor on time tumor response to therapy. Driven by the need, in this article we report nanoparticle surface energy transfer (NSET) approach to monitor photothermal therapy process by measuring the simple fluorescence intensity change. Florescence intensity change is due to the light-controlled photothermal release of ssDNA/RNA via dehybridization during therapy process. Our time dependent results show that just by monitoring fluorescence intensity change, one can monitor photothermal therapy response during therapy process. Possible mechanism and operating principle of our NSET assay have been discussed. Ultimately, this NSET assay could have enormous potential applications in rapid, on-site monitoring of photothermal therapy process, which is critical to providing effective treatment of cancer and MDRB infections.
In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies.
The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material.
Reverse phase protein microarray (RPPA) is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets.
With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification for individualized therapies.
Formalin-fixed; paraffin-embedded (FFPE); human epidermal growth factor receptor 2 (HER2); epidermal growth factor receptor 1 (EGFR); urokinase-type plasminogen activator (uPA); plasminogen activator inhibitor 1 (PAI-1); personalized cancer therapy; mitogen-activated protein kinase (MAPK)
Noninvasive molecular imaging using reporter genes is a relatively recent field in biomedical imaging that holds great promises for disease diagnosis and therapy. As modern medicine is moving towards personalized medicine, targeted biomolecule based therapies is gaining popularity that requires careful and systematic validation. Reporter genes have emerged as important generalizable tools to overcome the shortcomings of direct evaluation of individual biomolecules and are being applied in various fields such as cell therapy, stem cell therapy, immune therapy, viral gene delivery through optical, radionuclide, magnetic resonance imaging techniques. New approaches to image protein-protein interaction, protein phosphorylation, protein folding that are crucial parameters for theranostic study using reporter genes are being developed. All these new technologies and relevant preclinical and clinical researches will determine the success of early detection and personalized therapy in the future.
reporter genes; molecular imaging
Cancer continues to be one of the major health and socio-economic problems worldwide, despite considerable efforts to improve its early diagnosis and treatment. The identification of new constituents as biomarkers for early diagnosis of neoplastic cells and the discovery of new type of drugs with their mechanistic actions are crucial to improve cancer therapy. New drugs have entered the market, thanks to industrial and legislative efforts ensuring continuity of pharmaceutical development. New targets have been identified, but cancer therapy and the anti-cancer drug market still partly depend on anti-mitotic agents. The objective of this paper is to show the effects of KAR-2, a potent anti-mitotic compound, and TPPP/p25, a new unstructured protein, on the structural and functional characteristics of the microtubule system. Understanding the actions of these two potential effectors on the microtubule system could be the clue for early diagnosis and improvement of cancer therapy.
cancer; anti-mitotic drug; KAR-2; bioavailability; anti-mitotic protein; TPPP/p25
Discoveries in the pre-clinical neurosciences have set the stage for bringing new therapies to patients affected by neurological disorders. The National lnstitute of Neurological Disorders and Stroke (NINDS) is dedicated to promoting the development of new therapies through its funding programs that range from basic neuroscience to translational research and finally clinical research to test the most promising new therapies in patients. In an effort to accelerate the translation of new discoveries to clinical practice, NINDS is piloting novel organizational strategies. In translational research, NINDS is taking the lead on the establishment of a ‘virtual pharma' structure, through which researchers will partner with the NIH to accelerate the progress of drug development from early hit discovery through phase 1 clinical trials. In clinical research, the new Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) aims to promote the efficient implementation of scientifically sound, biomarker-informed phase 2 clinical trials that can be initiated by academic or industry investigators.
The recent advent of consensus definitions for acute kidney injury (AKI) has led to improvement in epidemiology of this complex disease and facilitated the development of new diagnostic makers and new therapies. However, important new challenges are also apparent. We still do not really understand why AKI occurs and urgently need to develop new therapies to treat it. Progress in this area will require new ideas and thinking outside the conventional box. By confronting some of the most significant controversies in the field of AKI we seek to develop new concepts that will ultimately yield new results.
Non-pharmacological, non-surgical interventions are recommended as the first line of treatment for osteoarthritis (OA) of the hip and knee. There is evidence that exercise therapy is effective for reducing pain and improving function in patients with knee OA, some evidence that exercise therapy is effective for hip OA, and early indications that manual therapy may be efficacious for hip and knee OA. There is little evidence as to which approach is more effective, if benefits endure, or if providing these therapies is cost-effective for the management of this disorder. The MOA Trial (Management of OsteoArthritis) aims to test the effectiveness of two physiotherapy interventions for improving disability and pain in adults with hip or knee OA in New Zealand. Specifically, our primary objectives are to investigate whether:
1. Exercise therapy versus no exercise therapy improves disability at 12 months;
2. Manual physiotherapy versus no manual therapy improves disability at 12 months;
3. Providing physiotherapy programmes in addition to usual care is more cost-effective than usual care alone in the management of osteoarthritis at 24 months.
This is a 2 × 2 factorial randomised controlled trial. We plan to recruit 224 participants with hip or knee OA. Eligible participants will be randomly allocated to receive either: (a) a supervised multi-modal exercise therapy programme; (b) an individualised manual therapy programme; (c) both exercise therapy and manual therapy; or, (d) no trial physiotherapy. All participants will continue to receive usual medical care. The outcome assessors, orthopaedic surgeons, general medical practitioners, and statistician will be blind to group allocation until the statistical analysis is completed. The trial is funded by Health Research Council of New Zealand Project Grants (Project numbers 07/199, 07/200).
The MOA Trial will be the first to investigate the effectiveness and cost-effectiveness of providing physiotherapy programmes of this kind, for the management of pain and disability in adults with hip or knee OA.
Australian New Zealand Clinical Trials Registry ref: ACTRN12608000130369.
This study used population-based tumor registry data to describe the patterns of adjuvant hormone therapy and to examine the correlates of hormone therapy for women with breast cancer. The study population included 5101 women (age 20 years) who were diagnosed with breast cancer in 1991 through 1997 in the entire state of New Mexico. Overall, 32% of women with stage I, II, or IIIA breast cancer received adjuvant hormone therapy. The likelihood of receiving adjuvant hormone therapy increased with tumor stage at diagnosis. Women less than 50 years of age were significantly less likely to receive adjuvant hormone therapy compared to those age 50 to 54 years, but there was no significant difference in the use of adjuvant hormone therapy for women age 55 years and older. The use of adjuvant hormone therapy was influenced by hormone receptor status and lymph node status. Patients who received adjuvant chemotherapy were also more likely to receive adjuvant hormone therapy than those who did not. The use of adjuvant hormone therapy alone was relatively stable over time and the use of adjuvant chemotherapy alone increased, but the receipt of chemotherapy combined with hormone therapy decreased from 1991 to 1997. There was no significant difference with age in the use of adjuvant hormone therapy among 55-year-old women compared to those age 50 to 54 years, whereas women less than 50 years of age were significantly less likely to receive this therapy. The use of adjuvant hormone therapy varied significantly by tumor stage, lymph node status, hormone receptor status, and the receipt of adjuvant chemotherapy.
adjuvant therapy; breast cancer; chemotherapy; hormone therapy; population-based; women
In view of the limited success of available treatment modalities for breast cancer, alternative and complementary strategies need to be developed. The delineation of the molecular basis of breast cancer provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches for carcinoma of the breast have been developed. These approaches can be divided into six broad categories: (1) mutation compensation, (2) molecular chemotherapy, (3) proapoptotic gene therapy, (4) antiangiogenic gene therapy, (5) genetic immunopotentiation, and (6) genetic modulation of resistance/sensitivity. Clinical trials for breast cancer have been initiated to evaluate safety, toxicity, and efficacy. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified and advances in vector design are realized, gene therapy will play an increasing role in clinical breast cancer treatment.
breast cancer; gene therapy; immunotherapy; carcinogenesis; suicide gene therapy
The integration of targeted therapies such as Cetuximab to radiation therapy has revolutionized the management of head and neck cancers in the last decade. However, the use of targeted therapies raised several clinically relevant questions that have yet to be answered. These questions include the optimal patient and tumor profile for biologically targeted therapy, the optimal radiation fractionation to use with targeted therapies, how to integrate them into standard or new chemo-radiation regimens, their schedule and duration of administration, their toxicity and which direction to consider for novel targeted treatment. In this review, we will highlight several of these important issues, the clinical trials that are designed to address these issues and introduce some novel targeted therapies that may contribute to the improvement of the therapeutic ratio for head and neck cancer therapy.
Historically, first-line treatment of non-small-cell lung cancer (nsclc) has been based on giving a limited number of cycles of chemotherapy to achieve tumour response or stable disease. Patients are then observed without active therapy until disease progresses, at which point, subsequent lines of therapy are given. In recent years, two new concepts have been introduced to the management of nsclc: maintenance therapy and therapy with targeted agents. Maintenance therapy—with either a chemotherapeutic or biologic agent—is given immediately after first-line therapy to patients who have achieved tumour response or stable disease. Choice of therapy may include continuation of the agents included in the induction regimen or introduction of different agents (early second-line treatment) with the aim of preventing progression and prolonging progression-free survival. Targeted agents such as bevacizumab and erlotinib target critical molecular signalling pathways and provide several advantages over chemotherapy, including fewer toxicities and the possibility of a longer duration of therapy. This review examines the treatment options in all lines of therapy for metastatic nsclc, focusing particularly on targeted therapies that have been approved in the United States, Canada, or Europe.
Targeted therapies; non-small-cell lung cancer; nsclc; metastatic; maintenance
AIM: To compare the effectiveness of sequential therapy for Helicobacter pylori (H. pylori) infection with that of triple therapy of varying durations.
METHODS: The 460 patients enrolled in this study had H. pylori-associated gastritis or a gastric or duodenal ulcer. After screening, H. pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7, 10 or 14 d, or a new 10-d sequential therapy. Each of the 4 treatment groups included 115 patients. The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology.
RESULTS: The overall eradication rate was 81.0%, and eradication rates were 75.7% for 7-d conventional triple therapy, 81.9% for 10-d conventional triple therapy, 84.4% for 14-d conventional triple therapy, and 82.0% for 10-d sequential therapy. Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy (P = 0.416 and P = 0.405, respectively).
CONCLUSION: There are no significant differences between 10-d sequential eradication therapy for H. pylori and any duration of standard triple treatment in Korean patients.
Helicobacter pylori; Sequential therapy; Triple therapy; Gastric ulcer; Duodenal ulcer; Gastritis
Over the past 20 years, several proton beam treatment programs have been implemented throughout the United States. Increasingly, the number of new programs under development is growing. Proton beam therapy has the potential for improving tumor control and survival through dose escalation. It also has potential for reducing harm to normal organs through dose reduction. However, proton beam therapy is more costly than conventional x-ray therapy. This increased cost may be offset by improved function, improved quality of life, and reduced costs related to treating the late effects of therapy. Clinical research opportunities are abundant to determine which patients will gain the most benefit from proton beam therapy. We review the clinical case for proton beam therapy.
Proton beam therapy is a technically advanced and promising form of radiation therapy.
Clinical review; Neoplasms; Proton beam therapy; X-ray therapy
Long-term estrogen deprivation treatment for breast cancer can, in some patients, lead to the activation of alternate cellular pathways, resulting in the re-emergence of the disease. This is a distressing scenario for oncologists and patients, but recent intensive molecular and biochemical studies are beginning to unravel these pathways, revealing opportunities for new targeted treatments. Far from making present therapies redundant, these new discoveries open the door to novel combination therapies that promise to provide enhanced efficacy or overcome treatment resistance. Letrozole, one of the most potent aromatase inhibitors, is the ideal candidate for combination therapy; indeed, it is one of the most intensively studied aromatase inhibitors in the evolving combinatorial setting. Complementary to the use of combination therapy is the development of molecular tools to identify patients who will benefit the most from these new treatments. Microarray gene profiling studies, designed to detect letrozole-responsive targets, are currently under way to understand how the use of the drug can be tailored more efficiently to specific patient needs.
Adjuvant therapy; Aromatase inhibitors; Breast cancer; Combination therapy; Letrozole; Mechanism of resistance; Postmenopausal
Metabolic complications including diabetes mellitus (DM) have been associated with protease inhibitor (PI) therapy. Risk factors for the development of DM are not well-defined.
To determine risk factors for the development of new-onset DM in patients initiated on PI therapy.
A retrospective cohort study was conducted to identify predictors of developing DM in subjects started on PI therapy between January 1997 and January 2003. Diabetes cases were defined as physician documentation of DM in the outpatient medical chart and/or those subjects receiving an antidiabetic agent. Logistic regression was used to examine the relationship between new-onset DM and demographic characteristics, and between new-onset DM and total treatment days with PI therapy. Body mass index could not be entered into the model due to missing height measurements.
A total of 496 subjects on PI therapy were included, of which 18 (3.6%) developed DM. The mean age of the subjects was 43.4±9.4 years (range 19 to 77) and the mean duration of therapy was 3.0±1.9 years (range 0.17 to 7.9). In the multivariate model, older subjects were more likely to develop DM (OR 1.12, 95% CI 1.05 to 1.19; P=0.001). This corresponds to a 12% increased risk of DM for each one-year increase in age. Subjects that weighed more had an increased risk (OR 1.06, 95% CI 1.03 to 1.10; P=0.001), as did those belonging to a non-Aboriginal minority group when compared with Caucasians (OR 6.67, 95% CI 1.56 to 28.41; P=0.01). A longer duration of PI therapy was also significantly associated with developing DM (OR 1.52, 95% CI 1.07 to 2.17; P=0.02).
A longer duration of PI therapy is associated with an increased risk of developing DM. As with HIV-negative subjects, demographic characteristics such as age, weight and ethnicity were important predictors of developing DM in the present study.
Diabetes mellitus; Protease inhibitors; Risk factors